The proposed research will adapt the standardize for clinical use a direct, non-invasive method for measuring human cardiac and hepatic iron stores by the in vivo determination of magnetic susceptibitity. Measurement of magnetic susceptibility relies on a fundamental physical property of storage iron and will be free of the confounding influences which have limited the clinical usefulness of indirect estimates of human iron stores. This safe, rapid and readily applicable technique can now detect hepatic iron overload in hemochromatosis, even in the precirrhotic stage. Mathematical models have been developed to convert measurements of magnetic susceptibility into cardiac or hepatic iron concentrations. These detailed models can incorporate numerical data derived from ultrasonic observations of the liver and time dependent quantitative measures of ventricular dimensions and motion derived from cross-sectional echocardiographic scanning. Using the specially designed superconducting magnetic gradiometer described in this proposal, it is estimated that differences in hepatic or cardiac iron concentrations of 50 micron g Fe/gm tissue or less will be detectable by serial measurements in a single individual. This level of sensitivity is sufficient to detect short term changes in hepatic iron stores produced by iron accumulation (absorption, transfusion) or iron excretion (chelation therapy) under current management regimens in thalassemia major. Measurement of magnetic susceptibility will provide the first in vivo means of directly studying the effects of transfusion or chelation therapy on cardiac iron deposits, an unresolved problem of critical importance in the treatment of thalassemia major.